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  • 1.

    【2hr】Comparison of a clinical-laboratory algorithm, 4t and heparin-induced thrombocytopenia expert probability scores in the diagnosis of heparin-induced thrombocytopenia in the critical care setting

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    机译 在重症监护环境中比较临床实验室算法，4t和肝素诱导的血小板减少症专家概率分数对肝素诱导的血小板减少症的诊断
    摘要：Background: Several scoring systems are utilized to calculate the pre-test probability of heparin-induced thrombocytopenia (HIT). We hypothesize that a clinical-laboratory algorithm combining the 4Ts score with the optical density (OD) of anti-PF4-heparin antibody is more accurate than either the 4Ts or HIT expert probability (HEP) scores in the critical care setting. Methods: A single-institution retrospective review of adult patients admitted to the intensive care unit (ICU) that were evaluated for HIT was conducted. Two reviewers independently rated the proposed algorithm, 4Ts and HEP score. Summary, univariate and area under receiver operator characteristic analyses were performed. Results: A total of 88 patients with a mean (SD) age of 62 (15) years were included. The sensitivity, positive predictive value and negative predictive value were superior in our clinical-laboratory algorithm compared to the 4Ts score ≥ 4 and the HEP score ≥ 2. The algorithm’s specificity was non-inferior to the 4Ts score and HEP score. There was no significant difference between our clinical-laboratory algorithm and the 4Ts score or the HEP score in predicting HIT. Conclusion: Our study confirms that the combination of clinical and laboratory criteria is crucial in the presumable diagnosis of HIT. This is the first study that validates different HIT scores in an isolated ICU population.
  • 2.

    【2hr】Partial pressure of oxygen in the human body: a general review

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    机译 人体氧分压：综述
    摘要：The human body is a highly aerobic organism, in which it is necessary to match oxygen supply at tissue levels to the metabolic demands. Along metazoan evolution, an exquisite control developed because although oxygen is required as the final acceptor of electron respiratory chain, an excessive level could be potentially harmful. Understanding the role of the main factors affecting oxygen availability, such as the gradient of pressure of oxygen during normal conditions, and during hypoxia is an important point. Several factors such as anaesthesia, hypoxia, and stress affect the regulation of the atmospheric, alveolar, arterial, capillary and tissue partial pressure of oxygen (PO2). Our objective is to offer to the reader a summarized and practical appraisal of the mechanisms related to the oxygen’s supply within the human body, including a facilitated description of the gradient of pressure from the atmosphere to the cells. This review also included the most relevant measuring methods of PO2 as well as a practical overview of its reference values in several tissues.
  • 3.

    【2hr】Patched homolog 1 (PTCHI) gene mutations can predict the outcome of chronic myeloid leukemia patients?

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    机译 修补的同源1（PTCHI）基因突变可以预测慢性粒细胞白血病患者的预后吗？
    摘要：Background: The Hedgehog (Hh) pathway is stimulated by inactivating mutations of Patched Homolog 1 (PTCH1) gene. There is accumulating evidence that Hh signaling plays a critical role in the pathogenesis of various haemopoietic malignancies. Particular interest has focused on the role of Hh signaling in chronic myeloid leukemia (CML). The Hh signaling is increased in BCR-ABL+ve progenitor cells and Hh signaling is further up regulated with disease progression. Aim: The aim of this study was to determine the frequency and types of PTCH1 gene mutations in Chronic Myeloid Leukemia (CML) patients and to correlate the effect of these mutations on the prognosis and outcome of CML and for predicting the imatinib response in CML patients. Subjects and methods: The study included fifty newly diagnosed CML patients and ten healthy volunteers (the control group) to verify the presence or absence of PTCH1 gene mutation. The patients were subjected to clinical examination, routine laboratory investigations, bone marrow examination, Cytogenetic evaluations of t(9;22) and molecular study of BCR-ABL fusion gene. All participants in this study were subjected to the assessment for the presence of PTCH1 gene mutation by DNA extraction followed by polymerase chain reaction (PCR) of genomic DNA corresponding to exon 23 of PTCH1 gene, purification of amplified PCR product, followed by sequencing analysis for detection of PTCH1 gene exon 23 mutations and the types of these mutations. Results: Four types of mutations of PTCH1 gene were detected in 24 CML patients (48%), three types of them were missence while the fourth type was frame shift mutation. There was no significant association between PTCH1 gene mutation and percent of BCR-ABL fusion genes at level less than 10% at 3 months of treatment, complete cytogenetic response (CCyR) at one year, disease free survival and overall survival. However there was significant association between PTCH1 gene mutation and imatinib failure (P=0.03). Conclusion: PTCH1 gene mutation should be considered a promising molecular marker for predicting the probability of imatinib response in CML patients. Hedgehog pathway activation in CML patients can raise a possibility that combinations of ABL and Hh inhibitors might offer a new treatment strategy in CML and might help to effectively cure this disease.
  • 4.

    【2hr】Advances in biology of acute lymphoblastic leukemia (ALL) and therapeutic implications

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    机译 急性淋巴细胞白血病（ALL）的生物学进展及其治疗意义
    摘要：Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and also occurs in adults. Although the outcomes of multi-agent chemotherapy regimens have greatly improved, high toxicity and relapses in many patients necessitate the development of novel therapeutic approaches. Advances in molecular profiling and cytogenetics have identified a broad range of genetic abnormalities, including gene mutations, chromosome translocations and aneuploidy, which has provided a more comprehensive understanding of the biology and pathogenesis of ALL. This understanding has also led to new targeted therapeutic approaches, including the use of selective small molecule inhibitors, nucleic acid-based therapies and immune-based therapies mediated by specific monoclonal antibodies and cellular immunotherapy, which are poised to revolutionize the treatment of various ALL subtypes. The main focus of this review is to highlight the latest advances in ALL biology, including the identification of prognostic factors and putative therapeutic targets. We also review the current status of, and ongoing progress in, the development of targeted therapies for ALL.
  • 5.

    【2hr】Use of direct oral anticoagulants in daily practice

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    机译 在日常实践中使用直接口服抗凝药
    摘要：In recent years, the options for anticoagulant therapy have examined new direct oral anticoagulants (DOACs) comprising direct thrombin inhibitors (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban). These agents represent further progress towards the ideal anticoagulant drug and thus towards a safe and effective antithrombotic therapy. The ideal anticoagulant is oral and has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects, and minimal interactions with other drugs or food. This review addresses the practical considerations for physicians in DOAC use, including indication, dosage, monitoring, pharmacokinetic profile, drug-drug interaction, and reversal of direct anticoagulation effects in case of bleeding.
  • 6.

    【2hr】An isolated der(1;21)(q10;q10) translocation in a patient with myelodysplastic syndrome: a case report

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    机译 骨髓增生异常综合症患者孤立的der（1; 21）（q10; q10）易位：一例
    摘要：Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on myeloid malignancies harboring der(1;21)(q10;q10). A 65-year-old male was referred to our hospital due to squamous cell carcinoma of the lung. Pembrolizumab monotherapy resulted in progression, and so chemotherapy involving nab-paclitaxel and carboplatin was administered thereafter. The patient developed cytopenia, and his bone marrow exhibited dysplasia. Chromosomal analysis revealed a whole-arm translocation, der(1;21)(q10;q10). Thus, the patient was diagnosed with myelodysplastic syndrome. The der(1;21)(q10;q10) translocation is a rare variant of the der(1;7)(q10;p10) translocation, which is an adverse prognostic factor for myeloid neoplasms. Clarifying the clinical features of myeloid neoplasms in patients with der(1;21)(q10;q10) would facilitate the elucidation of their tumorigenic mechanisms.
  • 7.

    【2hr】Comparing serum levels of zinc, copper, certain antioxidant vitamins and dietary intakes in acute lymphoblastic leukemia (ALL) patients before and after chemotherapy

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    机译 比较急性淋巴细胞白血病（ALL）化疗前后的血清锌，铜，某些抗氧化剂维生素和饮食摄入量
    摘要：Acute lymphoblastic leukemia (ALL) is a malignant hematologic disease. Cancer and its treatments can affect biological functions and change the nutritional status of patients. Zinc and copper are important cofactors for several enzymes and play an important role in maintaining the integrity of DNA. In ALL, we have oxidative conditions in the body that can cause oxidative damage to lipids and the production of malondialdehyde (MDA). So that the aim of this study is comparing serum levels of copper, zinc and inflammation before and after chemotherapy. Thirty ALL patients between 15 to 65 years old participated in this study. A blood sample of 10 cc was taken before and after eight course of chemotherapy. We observed a significant increase in serum zinc as well as a significant decrease in serum copper, vitamin D and Malondialdehyde. We have not seen any significant differences in hs-CRP after chemotherapy. These changes might be due to chemotherapy and changing lifestyle of patients toward healthy eating nutrition and serum vitamin D get worse and because of sedentary life style in these patients there is an essential need to anthropometric measurements during treatment.
  • 8.

    【2hr】Trisomy 6 as the sole stemline abnormality in a patient with acute monocytic leukemia: a case report

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    机译 6三体综合征是急性单核细胞白血病患者唯一的干系异常：一例报告
    摘要：It is rare for trisomy 6 to occur as the sole autosomal anomaly in hematological malignancies, but this finding has been reported to be associated with a hypoplastic bone marrow. We report the case of a 75-year-old male with acute monocytic leukemia, in which trisomy 6 was detected as the sole stemline abnormality. We also summarize the 26 published cases of acute myeloid leukemia involving isolated trisomy 6.
  • 9.

    【2hr】Comparison of DNA demethylating and histone deacetylase inhibitors hydralazine-valproate versus vorinostat-decitabine incutaneous t-cell lymphoma in HUT78 cells

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    机译 HUT78细胞中DNA脱甲基和组蛋白脱乙酰基酶抑制剂肼苯哒嗪-丙戊酸盐与伏立诺他-地他滨皮肤性T细胞淋巴瘤的比较
    摘要：Purpose: Cutaneous T-cell lymphoma (CTCL) is an uncommon extranodal non-Hodgkin T-cell lymphoma that originates from mature T lymphocytes homed at the skin. Epigenetic alterations observed in CTCL are not limited to overexpression of Histone Deacetylases but also to DNA hypermethylation. The known synergy between Histone deacetylase inhibitors (HDACi) and DNA methyltransferases inhibitors (DNMTi) suggests that combining these agent classes could be effective for CTCL. Methods: In this study, the combinations of the HDACi and DNMTi hydralazine/valproate (HV) and vorinostat/decitabine (VD) were compared in regard to viability inhibition, clonogenicity, pharmacological interaction and cell cycle effects in the CTCL cell line Hut78. In addition, the effect of these combinations was evaluated in normal peripheral blood mononuclear cells. Results: The results show that each of the DNMTi and HDACi exerts growth inhibition, mostly by inducing apoptosis as shown in the cell cycle distribution. However, in the combination of HV the interaction is more synergic and also it inhibits the clonogenic capacity of cells over time. Additionally, the HV combination seems to affect in a minor degree the viability of peripheral blood mononuclear cells. Conclusions: The results of this study and the preclinical and clinical evidence on the efficacy of combining HDACi with DNMTi strongly suggest that more studies are needed with this drug class combination in CTCL, particularly with the hydralazine-valproate scheme, which is safe, and these drugs are widely available and administered by oral route.
  • 10.

    【2hr】Cytogenetic study is not essential in patients with aplastic anemia

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    机译 再生障碍性贫血患者的细胞遗传学研究不是必需的
    摘要：Depending on contemporary treatment approach of aggressive immunosuppression, Aplastic Anemia (AA) is caused by immunological destruction of otherwise normal hematopoietic stem cells. The aim was to summarize the cytogenetic abnormalities in AA patients and the frequency of Fanconi Anemia (FA) in morphologically normal AA patients in eastern India. Ethical clearances were obtained from both institutions involved in this study. Out of 72800 patients attending the outpatient department, 520 pancytopenia patients were screened for AA after Bone marrow (BM) aspiration and biopsy. Samples were collected from 117 cases in 3 phases. 51 peripheral venous blood (PVB) samples in the first phase, 19 BM & PVB paired samples in the second phase and 47 BM samples in third phase were collected followed by leukocyte and/or BM stem cell culture. Next GTG banding and karyotyping were performed. PVB was collected from 63 (< 50 years) AA patients and stress cytogenetics was done to diagnose FA. In the first phase of the study, out of 51 PVB samples, 1 (1.96%) showed a unique chromosomal abnormality, i.e. 45,XY,rob(14:21)(p10:q10)[20]. In the second phase of study, among 19 BM & PVB paired samples, 1 (5.26%) showed abnormal karyotype i.e. 45,X,-Y[3]/46,XY[47]. In the third phase of the study, 47 BM samples showed normal karyotype. Only 6 (9.52%) cases were found positive for stress cytogenetics. A negligible percentage showing cytogenetic abnormality in such a considerable number of AA cases indicates that routine cytogenetic analysis of AA patient is not essential. A significant percentage was positive for stress cytogenetics; suggestive for FA, even the patients were morphologically normal.
  • 11.

    【2hr】Evaluation of bone mineral density and related parameters in patients with haemophilia: a single center cross-sectional study

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    机译 血友病患者骨矿物质密度和相关参数的评估：单中心横断面研究
    摘要：Haemophilia has been associated with low bone mineral density (BMD) probably due to some predisposing factors. The aim of this study was to evaluate the relationship between BMD and potential clinical predictors in adult haemophilic patients. Fortynine patients with moderate and severe haemophilia were enrolled. BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were performed for vitamin D, calcium, phosphore, alkaline phosphatase and parathormone levels. Functional Independence Score in Haemophilia (FISH) and Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency virus (HIV) seropositivity and smoking status were also recorded. BMD was found lower than expected for reference age in 34.8% of patients of less than 50 years old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of them had normal BMD. FISH score was statistically significant correlated with BMD of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible patients, there was also a statistically significant correlation between BMD of TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients, although there was no significant correlation with BMD. Also no correlation was found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study confirmed that patients with haemophilia have an increased prevelance of low BMD even in younger group. Our results showed that there are significant correlations between FISH score and BMD of TH and FN and also between HJHS score and BMD of TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD to reflect the severity of haemophilic arthropathy.
  • 12.

    【2hr】Factors affecting the body mass index, haemoglobin and serum ferritin level in students

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    机译 影响学生体重指数，血红蛋白和血清铁蛋白水平的因素
    摘要：Ferritin is a protein found in reticuloendothelial system and does not work only as a mid-size protein during Hemoglobin synthesis but also as storage protein for iron delivery. This cross sectional study was conducted in District Shaheed Benazirabad during the period of August 2015 to March 2016, for obtaining credible and consolidated data. In present study we investigated BMI, Hb and S.f level with relation to socioeconomic status in children and adults from total 2040 volunteers (girls n=991, boys n=1049). The questionnaire included education, social class, age, sex, and information about dietary habits. Blood samples were collected & assessed by ELISA method and sysmex hemoglobin auto analyzer instrument for serum ferritin and hemoglobin level. The mean value of Body Mass index, the average value of hemoglobin and serum ferritin level was observed accordingly 18.6, 12.1 g/dl, 82.8 μg/l in all samples. It was concluded that monthly income of the volunteers have significant association with Hb, BMI and Serum ferritin at the P<0.01 level. However, environmental conditions, blood loss in females during menstruation, low maternal attention, socioeconomic and dietary habits are main factors which affect the BMI, Hb and S.f level in students.
  • 13.

    【2hr】Efficacy and safety of ClairYg®, a ready-to-use intravenous immunoglobulin, in adult patients with primary immune thrombocytopenia

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    机译 即用型静脉免疫球蛋白ClairYg®在成年原发性免疫性血小板减少症患者中的疗效和安全性
    摘要：Purpose: The present study was designed to assess the efficacy and safety of IGNG that is a new liquid, saccharose and maltose-free highly purified ready-to-use 5% intravenous immunoglobulin (IVIg), in primary immune thrombocytopenic patients with severe thrombocytopenia.Methods: Nineteen adults with a platelet count ≤ 25 × 109/L received a single dose of IGNG (1 g/kg) on Day 1, with a second identical dose on Day 3 if needed. Patients were followed for 30 days. Primary endpoint was the response rate, defined as the proportion of patients with a platelet count ≥ 50 × 109/L within 96 hours after the first IGNG dose.Results: All but one of the 17 evaluable patients for efficacy responded with an overall response rate of 94.1% (95% CI 71.3%-99.9%). Response was observed after only one infusion (1 g/kg body weight) in 11 patients (65%) and the others required a second dose. Mean time to response was 2.2 days. Maximum platelet count was reached within 1 week after the first dose and lasted for approximately 2 weeks. Patients requiring a second dose had lower platelet counts at baseline than patients requiring a single dose. In the 19 evaluable patients for safety, IGNG demonstrated good safety, good hepatic and renal tolerance, and did not induce hemolysis. This trial was registered at the French Medical Agency (AFSSAPS) as #DI n°060735.
  • 14.

    【2hr】Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma, a diagnostic challenge

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    机译 伴随性浆细胞性淋巴瘤和浆细胞骨髓瘤，诊断上的挑战
    摘要：Background: Lymphoplasmacytic lymphoma and plasma cell myeloma are two B cell lymphoproliferative neoplasms derived from mature B-lymphocytes in different differentiation stages. The coexistence of these two tumors in the same patient is exceedingly rare and can be difficult to diagnose. Case presentation: A 76-year-old male presented with a pathologic fracture after a fall. Radiography showed a lytic lesion in the pelvis. Serum immunofixation showed distinct IgM kappa and IgA kappa monoclonal protein bands. Bone marrow examination revealed aggregates of small, mature lymphoid cells with admixed plasma cells. Immunohistochemical studies and flow cytometric analysis showed the lymphoid cells were CD10-/CD5- kappa restricted monoclonal B cells. The plasma cells were monoclonal with kappa light chain restriction. The majority of plasma cells were positive for IgA and cyclin D1 with a few plasma cells positive for IgM. Additional studies showed the presence of both a positive MYD88 L265P mutation and a CCND1/IGH fusion. A diagnosis of concomitant lymphoplasmacytic lymphoma and plasma cell myeloma was rendered. Conclusion: Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma can be rarely encountered and is diagnostic challenging. It is commonly associated with biclonal monoclonal proteins. This case demonstrates the importance of a comprehensive work-up in the diagnosis of this disease combination and highlights the diagnostic role of MYD88 mutation study.
  • 15.

    【2hr】Efficacy and safety of ClairYg®, a ready-to-use intravenous immunoglobulin, in adult patients with primary immune thrombocytopenia

    包量

    机译 即用型静脉免疫球蛋白ClairYg®在成年原发性免疫性血小板减少症患者中的疗效和安全性
    摘要：Purpose: The present study was designed to assess the efficacy and safety of IGNG that is a new liquid, saccharose and maltose-free highly purified ready-to-use 5% intravenous immunoglobulin (IVIg), in primary immune thrombocytopenic patients with severe thrombocytopenia. Methods: Nineteen adults with a platelet count ≤ 25 × 109/L received a single dose of IGNG (1 g/kg) on Day 1, with a second identical dose on Day 3 if needed. Patients were followed for 30 days. Primary endpoint was the response rate, defined as the proportion of patients with a platelet count ≥ 50 × 109/L within 96 hours after the first IGNG dose. Results: All but one of the 17 evaluable patients for efficacy responded with an overall response rate of 94.1% (95% CI 71.3%-99.9%). Response was observed after only one infusion (1 g/kg boby weight) in 11 patients (59%) and the others required a second dose. Mean time to response was 2.2 days. Maximum platelet count was reached within 1 week after the first dose and lasted for approximately 2 weeks. Patients requiring a second dose had lower platelet counts at baseline than patients requiring a single dose. In the 19 evaluable patients for safety, IGNG demonstrated good safety, good hepatic and renal tolerance, and did not induce hemolysis. This trial was registered at the French Medical Agency (AFSSAPS) as #DI n°060735.
  • 16.

    【2hr】Treatment of older patients with acute myeloid leukemia (AML): revised Canadian consensus guidelines

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    机译 老年急性髓性白血病（AML）的治疗：修订的加拿大共识指南
    摘要：The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT). Midostaurin should be added to induction therapy for patients up to age 70 with a FLT3 mutation, and gemtuzumab ozogamicin for de novo AML up to age 70 with favorable or intermediate risk cytogenetics. Daunorubicin 60 mg/m2 is the recommended dose for 3+7 induction therapy. Acute promyelocytic leukemia should be treated with arsenic trioxide plus all-trans retinoic acid, regardless of age, with cytotoxic therapy added upfront only for those with initial white blood count > 10. HSCT may be considered for selected suitable patients up to age 70-75. Haploidentical donor transplants may be considered for older patients. For non-induction candidates, azacitidine is recommended for those with adverse risk cytogenetics, while either a hypomethylating agent (HMA) or low-dose cytarabine can be used for others. HMA may also be used for relapsed/refractory disease after chemotherapy. For patients with secondary AML, CPX-351 is recommended for fit patients age 60-75.
  • 17.

    【2hr】Luminol-amplified chemiluminescence detects mainly superoxide anion produced by human neutrophils

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    机译 鲁米诺扩增的化学发光主要检测人嗜中性粒细胞产生的超氧阴离子
    摘要：Reactive oxygen species (ROS) are produced by numerous biological systems and by several phagocytes such as neutrophils and macrophages. ROS include mostly superoxide anion, hydrogen peroxide, singlet oxygen and hydroxyl radical, which are involved in a variety of biological processes such as immunity, inflammation, apoptosis and cell signaling. Thus, there is a need for a sensitive and reliable method to measure ROS. The luminol-amplified chemiluminescence technique is widely used to measure ROS production by neutrophils; however, it is unclear which ROS species are detected by this technique. In this study, we show that Xanthine/Xanthine oxidase (XXO), a known superoxide-producing system, stimulated a luminol-amplified chemiluminescence in the absence of horseradish peroxidase (HRPO), while the presence of HRPO enhanced the response. Both reactions were inhibited by superoxide dismutase (SOD), but not by catalase, confirming that superoxide anion, and not hydrogen peroxide, is the species oxidizing luminol to produce chemiluminescence. Glucose/Glucose oxidase (GGO), a known hydrogen peroxide-producing system, did not induce luminol-amplified chemiluminescence in the absence of HRPO; however, addition of HRPO resulted in a chemiluminescence response, which was inhibited by catalase, but not by SOD. Myeloperoxidase (MPO), isolated from human neutrophils, was also able to enhance the superoxide- and hydrogen peroxide-dependent luminol-amplified chemiluminescence. The production of ROS by stimulated human neutrophils was detected by luminol-amplified chemiluminescence, which was only partially inhibited by SOD and catalase. Interestingly, adding HRPO to stimulated neutrophils increased the luminol-amplified chemiluminescence, which was strongly inhibited by SOD, but not by catalase. These results show that (a) luminol-amplified chemiluminescence is able to detect superoxide anion in the absence of peroxidases, but not hydrogen peroxide; (b) in the presence of peroxidases, luminol-amplified chemiluminescence is able to detect both superoxide anion and hydrogen peroxide; and (c) luminol-amplified chemiluminescence detects mainly superoxide anion produced by neutrophils, especially in the presence of HRPO.
  • 18.

    【2hr】DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex

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    机译 DDX6将P-TEFb激酶转移至AF4 / AF4N（AFF1）超伸长复合物
    摘要：AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of “super elongation complexes” (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex. DDX6 is an evolutionarily conserved member of the DEAD-box RNA helicase family that is known to control miRNA and mRNA biology (translation, storage and degradation). Overexpressed DDX6 is associated with different cancer types and with c-Myc protein overexpression. We could demonstrate that DDX6 binds to 7SK snRNA and causes the release and transfer of P-TEFb to the AF4/AF4N SEC. DDX6 also binds stably to AF4 and AF4N as demonstrated by GST pull-down and co-immunoprecipitation experiments. As a consequence, overexpression of either AF4/AF4N or DDX6 resulted in a strong increase of mRNA production (5-6 fold), while their simultaneous expression increased the cellular mRNA production by 11-fold. Conversely, the corresponding knockdown of DDX6 decreased mRNA production by 70%. In conclusion, AF4/AF4N and DDX6 represent key molecules for the elongation process of gene transcription and a model will be proposed for the hand-over process of P-TEFb to SECs.
  • 19.

    【2hr】Pesg PNH diagnosis, follow-up and treatment guidelines

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    机译 Pesg PNH诊断，随访和治疗指南
    摘要：PNH Education and Study Group (PESG) have been established in December 2013 as a non-profit, independent, medical organization www.pesg.org. Paroxysmal Nocturnal Hemoglobinuria (PNH) is a multi-systemic disease that should be treated with a multidisciplinary approach. Patients may apply to the clinics other than the hematology due to variability and diversity of clinical findings which lower the rate of diagnosis due to low awareness about PNH. PNH might be overlooked and diagnosis might be delayed. Regarding these, PESG was established with the collaboration of Immunology, Cardiology, Thorax Diseases (Pulmonology), Neurology, Gastroenterology, General Surgery and Urology specialists in addition to hematologists dealing with PNH. The PESG study group aims to increase the awareness about PNH, including training activities about PNH, strengthening the relations between clinics and planning of clinical studies as a goal. It is the first professional organization focusing on PNH, in Turkey.In this guideline, we want to facilitate the diagnosis attributes of physicians from all specializations that deal with PNH and its systemic complications. One can perceive this as a tailor made guideline of international guidelines but not a compilation.
  • 20.

    【2hr】Methotrexate-associated primary cutaneous CD30-positive cutaneous T-cell lymphoproliferative disorder: a case illustration and a brief review

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    机译 甲氨蝶呤相关的原发性皮肤CD30阳性的皮肤T细胞淋巴组织增生性疾病：一例病例和简要回顾
    摘要：Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman. Patient had been on MTX for rheumatoid arthritis (RA) which was stopped after the patient was evaluated at our institution. Patient had an incredible response to stopping immunosuppression with spontaneous regression of skin lesions and disappearance of clonal malignant cell population as evidenced on serial biopsy specimens. Primary cutaneous CD30+ LPDs constitute about 30% of the primary cutaneous T-cell lymphomas (CTLs) and includes entities such as lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and other CD30+ borderline LPDs. Histopathological criteria in addition to CD30 positivity is important for identification of these conditions. Treatment options include “wait and see”, phototherapy, radiotherapy, topical agents, systemic therapy and surgical resection. Prognosis is excellent and most cases resolve spontaneously on withdrawal of immunosuppression. Refractory cases may require aggressive local treatment or systemic therapy. Brentuximab Vedontin, an anti-CD30 antibody drug conjugate (ADC), may provide additional therapeutic option in refractory cases.
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